An Effective Bacterial Fucosidase for Glycoprotein Remodeling

Tsai, Tsung-I; Li, Shiou-Ting; Liu, Chiu-Ping; Chen, Karen Y.; Shivatare, Sachin S.; Lin, Chang‐Yu; Liao, Shih-Fen; Lin, Chih-Wei; Hsu, Tsui-Ling; Tsai, Ming–Hung; Lai, Meng-Yu; Lin, Nan‐Horng; Wu, Chung‐Yi; Wong, Chi‐Huey

doi:10.1021/acschembio.6b00821

Cited by 38 publications

(30 citation statements)

References 49 publications

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“…Moreover, the organomercury PCMB severely inactivated the enzyme (Table 1), whereas this inhibitory effect on cFase I was reversible with additional DTT (data not shown). Our observations were similar to those in previous reports on fucosidases (42)(43)(44). Furthermore, the fucosidase-specific inhibitor deoxyfuconojirimycin inhibited the activity of cFase I, indicating the fucosidase activity of the enzyme (Fig.…”

Section: Enzymatic Characterization Of Cfase I With Pnpssupporting

confidence: 93%

Identification and characterization of a core fucosidase from the bacterium Elizabethkingia meningoseptica

Hou

et al. 2018

Journal of Biological Chemistry

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All reported α-l-fucosidases catalyze the removal of nonreducing terminal l-fucoses from oligosaccharides or their conjugates, while having no capacity to hydrolyze core fucoses in glycoproteins directly. Here, we identified an α-fucosidase from the bacterium with catalytic activity against core α-1,3-fucosylated substrates, and we named it core fucosidase I (cFase I). Using site-specific mutational analysis, we found that three acidic residues (Asp-242, Glu-302, and Glu-315) in the predicted active pocket are critical for cFase I activity, with Asp-242 and Glu-315 acting as a pair of classic nucleophile and acid/base residues and Glu-302 acting in an as yet undefined role. These findings suggest a catalytic mechanism for cFase I that is different from known α-fucosidase catalytic models. In summary, cFase I exhibits glycosidase activity that removes core α-1,3-fucoses from substrates, suggesting cFase I as a new tool for glycobiology, especially for studies of proteins with core fucosylation.

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Section: Enzymatic Characterization Of Cfase I With Pnpssupporting

confidence: 93%

Identification and characterization of a core fucosidase from the bacterium Elizabethkingia meningoseptica

Hou

et al. 2018

Journal of Biological Chemistry

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“…However, the increasing abundances of Lactobacillales and Bacteroidales spp. in both groups indicated the hydrolyzing ability of these bacteria on fucoses joined by different linkages, as some studies have revealed the core fucose hydrolyzing abilities of these bacteria (78, 79). Therefore, further molecular mechanical studies regarding to the effects of milk protein N-glycans on these gut microbes are needed.…”

Section: Discussionmentioning

confidence: 92%

Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages

Bai

Tao²,

Zhou

et al. 2018

mSystems

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Human milk glycans provide a broad range of carbon sources for gut microbes in infants. Levels of protein glycosylation in human milk vary during lactation and may also be affected by the stages of gestation and lactation and by the secretor status of the mother. This was the first study to evaluate systematically dynamic changes in human milk oligosaccharides and fucosylated N-glycans in the milk of Chinese mothers with different secretor statuses during 6 months of lactation. Given the unique single nucleotide polymorphism site (rs1047781, A385T) on the fucosyltransferase 2 gene among Chinese populations, our report provides a specific insight into the milk glycobiome of Chinese mothers, which may exert effects on the gut microbiota of infants that differ from findings from other study cohorts.

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“…However, compared with oligosaccharides, the structure of protein N-glycans is more complicated. Bacterium-derived fucosidases were reported to have very low activity in decomposing the α-1,6-bond core fucose (75). Fuc-α1,6-GlcNAc can only be hydrolyzed by α- l -fucosidases with the assistance of endo- N -acetylglucosidases (Endo), which hydrolyzes the N-glycans between two adjacent N-GlcNAc.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, use of synthetic Fuc-α1,6-GlcNAc and Fuc-α1,6-GlcNAc-GlcNAc by L. casei and L. gasseri suggests the coexpression of Endo and AflC-like enzymes in their genomes and their superiority when competing with other gut microbes. However, when Fuc-α1,6-GlcNAc was incubated with Bifidobacterium spp., no obvious growth-promoting effects were detected, although α- l -fucosidase genes were also found in the genomes of Bifidobacterium spp., but with poor activity for hydrolyzing the α1,6-linkage-bond fucose (75). Therefore, the substantially greater proportion of bifidobacteria in infants fed by mothers with high-core-fucosylated milk N-glycan may due to excreted l -fucose by Lactobacillus spp.…”

Section: Discussionmentioning

confidence: 99%

Core Fucosylation of Maternal Milk N-Glycan Evokes B Cell Activation by Selectively Promoting thel-Fucose Metabolism of GutBifidobacteriumspp. andLactobacillusspp

Bai

Zhou

et al. 2019

mBio

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The maternal milk glycobiome is crucial for shaping the gut microbiota of infants. Although high core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is a general feature of human milk glycoproteins, its role in the formation of a healthy microbiota has not been evaluated. In this study, we found that the core-fucosylated N-glycans in milk of Chinese mothers selectively promoted the colonization of specific gut microbial groups, such as Bifidobacterium spp. and Lactobacillus spp. in their breast-fed infants during lactation. Compared with Fut8+/+ (WT) mouse-fed neonates, the offspring fed by Fut8+/− maternal mice had a distinct gut microbial profile, which was featured by a significant reduction of Lactobacillus spp., Bacteroides spp., and Bifidobacterium spp. and increased abundance of members of the Lachnospiraceae NK4A136 group and Akkermansia spp. Moreover, these offspring mice showed a lower proportion of splenic CD19+ CD69+ B lymphocytes and attenuated humoral immune responses upon ovalbumin (OVA) immunization. In vitro studies demonstrated that the chemically synthesized core-fucosylated oligosaccharides possessed the ability to promote the growth of tested Bifidobacterium and Lactobacillus strains in minimal medium. The resulting L-fucose metabolites, lactate and 1,2-propanediol, could promote the activation of B cells via the B cell receptor (BCR)-mediated signaling pathway. IMPORTANCE This study provides novel evidence for the critical role of maternal milk protein glycosylation in shaping early-life gut microbiota and promoting B cell activation of neonates. The special core-fucosylated oligosaccharides might be promising prebiotics for the personalized nutrition of infants.

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An Effective Bacterial Fucosidase for Glycoprotein Remodeling

Cited by 38 publications

References 49 publications

Identification and characterization of a core fucosidase from the bacterium Elizabethkingia meningoseptica

Identification and characterization of a core fucosidase from the bacterium Elizabethkingia meningoseptica

Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages

Core Fucosylation of Maternal Milk N-Glycan Evokes B Cell Activation by Selectively Promoting thel-Fucose Metabolism of GutBifidobacteriumspp. andLactobacillusspp

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